Dataset Information

Disease-specific plasma levels of mitokines FGF21, GDF15, and Humanin in type II diabetes and Alzheimer's disease in comparison with healthy aging.

ABSTRACT: Fibroblast Growth Factor 21 (FGF21), Growth Differentiation Factor 15 (GDF15), and Humanin (HN) are mitochondrial stress-related mitokines, whose role in health and disease is still debated. In this study, we confirmed that their plasma levels are positively correlated with age in healthy subjects. However, when looking at patients with type 2 diabetes (T2D) or Alzheimer's disease (AD), two age-related diseases sharing a mitochondrial impairment, we found that GDF15 is elevated in T2D but not in AD and represents a risk factor for T2D complications, while FGF21 and HN are lower in AD but not in T2D. Moreover, FGF21 reaches the highest levels in centenarian' offspring, a model of successful aging. As a whole, these data indicate that (i) the adaptive mitokine response observed in healthy aging is lost in age-related diseases, (ii) a common expression pattern of mitokines does not emerge in T2D and AD, suggesting an unpredicted complexity and disease-specificity, and (iii) FGF21 emerges as a candidate marker of healthy aging.

SUBMITTER: Conte M

PROVIDER: S-EPMC8110619 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Disease-specific plasma levels of mitokines FGF21, GDF15, and Humanin in type II diabetes and Alzheimer's disease in comparison with healthy aging.

Conte Maria M Sabbatinelli Jacopo J Chiariello Antonio A Martucci Morena M Santoro Aurelia A Monti Daniela D Arcaro Marina M Galimberti Daniela D Scarpini Elio E Bonfigli Anna Rita AR Giuliani Angelica A Olivieri Fabiola F Franceschi Claudio C Salvioli Stefano S

GeroScience 20201031 2

Fibroblast Growth Factor 21 (FGF21), Growth Differentiation Factor 15 (GDF15), and Humanin (HN) are mitochondrial stress-related mitokines, whose role in health and disease is still debated. In this study, we confirmed that their plasma levels are positively correlated with age in healthy subjects. However, when looking at patients with type 2 diabetes (T2D) or Alzheimer's disease (AD), two age-related diseases sharing a mitochondrial impairment, we found that GDF15 is elevated in T2D but not in ...[more]

PMID: 33131010

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Project description:ImportanceIdentifying novel factors that protect against age-related diseases and promote healthy aging is critical to public health. Higher levels of circulating very-long-chain saturated fatty acids (VLSFAs) are integrated biomarkers of diet and metabolism shown to have beneficial associations in cardiovascular disease and total mortality, but whether they are associated with overall healthy aging is unknown.ObjectiveTo examine the association of circulating levels of 3 VLSFAs with unhealthy aging events, including incident chronic disease (cardiovascular disease, cancer, lung disease or severe kidney disease), physical dysfunction, and cognitive decline.Design, setting, and participantsThis cohort study used 1992 to 2014 data from the Cardiovascular Health Study (CHS). The CHS is a multicenter, population-based study of cardiovascular disease among older adults. Among the 4559 CHS participants with available fatty acid data, 1879 participants who had an age-related event before their first measurement were excluded. Data analysis was performed in 2020.Main outcomes and measuresPlasma phospholipid VLSFA levels were measured by thin-layer chromatography followed by gas chromatography. The main outcome was the hazard ratio (HR) of an incident unhealthy aging event associated with serial measures of plasma arachidic acid, behenic acid, and lignoceric acid.ResultsAmong the 2680 study participants (976 men [36.4%]), the mean (SD) age was 74.7 (4.8) years old at entry. During a median (interquartile range) of 6.4 (2.9-12.9) years of follow-up, 2484 participants experienced an unhealthy event. Compared with the lowest quintile, levels of behenic acid in the highest quintile of the fatty acid distribution were associated with 15% lower risk of an unhealthy event (HR, 0.85; 95% CI, 0.74-0.97; P for trend = .01) after adjustment for demographic characteristics, lifestyle factors, and clinical conditions. In analogous comparisons, levels of lignoceric acid were similarly associated with 16% lower risk of an unhealthy event (HR, 0.84; 95% CI, 0.73-0.95; P for trend = .001).Conclusions and relevanceThese findings suggest that higher levels of circulating behenic acid and lignoceric acid are associated with lower risk of unhealthy aging events. These results highlight the need to explore determinants of circulating VLSFAs for potential novel efforts to promote healthy aging.

Dataset Information

Disease-specific plasma levels of mitokines FGF21, GDF15, and Humanin in type II diabetes and Alzheimer's disease in comparison with healthy aging.

Publications

Disease-specific plasma levels of mitokines FGF21, GDF15, and Humanin in type II diabetes and Alzheimer's disease in comparison with healthy aging.

Similar Datasets

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